The paradoxical role of methionine enkephalin in tumor responses

Eur J Pharmacol. 2020 Sep 5:882:173253. doi: 10.1016/j.ejphar.2020.173253. Epub 2020 Jun 11.

Abstract

Methionine enkephalin (MENK) is an opioid peptide composed of five amino acids with multiple biological activities. Since its discovery, MENK has become prominent in neuroregulation and immunoregulation. Tumors have increasingly been a spotlight because of their terrible trends and refractory characteristic. The therapeutic potential of MENK was investigated on a large scale, and there are numerous evidences that MENK exerts anti-tumor effects via two mechanisms. The first mechanism explains the enhanced anti-tumor immune effects of MENK. The second mechanism shows that MENK directly inhibits tumor cell proliferation. However, numerous reports have clarified the pro-tumor role of MENK by inhibiting T and B cell proliferation, promoting tumor cell growth by binding to opioid receptors, leading to desensitization of lymphocytes, and inducing tolerance. It is particularly intriguing that dual reactions are triggered when MENK combines with its opioid receptors; thus, anti-tumor response of the whole body is influenced. This review will expound the dual roles of MENK in tumor responses based on immune cells, cytokines, and tumor cells to provide better suggestions for its application in tumor treatment.

Keywords: Cytokines; Immune cells; Methionine enkephalin; Opioid receptors; Tumor.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Enkephalin, Methionine / pharmacology
  • Enkephalin, Methionine / therapeutic use*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism

Substances

  • Antineoplastic Agents
  • Enkephalin, Methionine